Marriage has been a hot topic since ancient times forever, yet there is little research evidence on marital status as an important socio-behavioral fa…

Cells can enter a stress response state termed cellular senescence that is involved in various diseases and aging. Detecting these cells is challenging due to the lack of universal biomarkers. This r...

Neurodegenerative diseases (NDDs) pose significant challenges in early detection and treatment due to their complex pathophysiology and heterogeneous clinical presentations. MicroRNAs (miRNAs), small noncoding RNAs that regulate gene expression, have emerged as promising diagnostic biomarkers and therapeutic targets in NDDs. Pathological examination of affected tissues reveals early synaptic dysfunction, protein misfolding, and neuroinflammation occur prior to overt clinical symptoms, highlighting the importance of sensitive diagnostics approaches in prodromal stages. This review summarizes for researchers on the role of miRNAs in NDDs by examining their diagnostic potential in biofluids such as blood and cerebrospinal fluid, and their therapeutic applicability through inhibition or replacement strategies. Literature from peer-reviewed databases was assessed with a focus on recent advances in molecular detection platforms, computational modeling of miRNA–mRNA interactions, and preclinical/clinical investigations.More than 2600 human miRNAs have been identified, collectively regulating over half of mammalian protein-coding genes. Quantitative methodologies, particularly reverse transcription quantitative PCR (RT-qPCR), enable reliable miRNA profiling, facilitating early diagnosis and prognosis of NDDs. Therapeutic strategies, including antagomirs, mimics, sponges and viral or non-viral delivery systems, show promise in modulating disease pathways. However, significant challenges remain, including variability in miRNA extraction and quantification protocols, off-target effects, delivery barriers across the blood brain barrier and limited reproducibility across studies. MiRNAs represent a class of molecular tools with potential to transform diagnostics and therapeutics in NDDs. Future research should prioritize methodological standardization, validation in large multicenter cohorts, and improved computational approaches to elucidate miRNA-mediated regulatory networks in NDDs. Replication studies and translational research are essential harnessing the the full clinical utility of miRNAs in the management of Alzheimer disease, Parkinson disease and other NDDs.

Background Accelerated aging is a dynamic process, yet few studies examined the association of changes in accelerated aging with cardiovascular disease (CVD) and mortality. This study aims to evaluate this association in three prospective cohorts from China and the UK. Methods Data were drawn from the Kailuan cohort (n = 107,830), the Dongfeng-Tongji (DFTJ) cohort (n = 14,032), and the UK Biobank (n = 316,087). Accelerated aging was assessed by PhenoAge and Klemera-Doubal method (KDM) age, measured at baseline (Kailuan cohort: 2006–2009; DFTJ cohort: 2008–2010; UK Biobank: 2006–2010) and the first follow-up (Kailuan cohort: 2010–2013; DFTJ cohort: 2013; UK Biobank: 2012–2013). Changes in accelerated aging were classified as persistent accelerated aging, recovery from accelerated aging, delayed accelerated aging, and stable non-accelerated aging. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Meta-analysis was performed to summarize estimates across three cohorts. Results Median follow-up periods were 10.3–15.9 years across three cohorts. When defining accelerated aging by PhenoAge, baseline accelerated aging was significantly associated with increased risks of CVD (pooled HR: 1.41, 95% CI: 1.25, 1.60) and mortality (pooled HR: 1.47, 95% CI: 1.33, 1.63). Compared to participants with persistent accelerated aging, participants recovering from accelerated aging (pooled HR of CVD: 0.76, 95% CI: 0.72, 0.81; pooled HR of mortality: 0.84, 95% CI: 0.78, 0.89), delaying accelerated aging (pooled HR of CVD: 0.75, 95% CI: 0.70, 0.79; pooled HR of mortality: 0.77, 95% CI: 0.72, 0.83) or maintaining non-accelerated aging (pooled HR of CVD: 0.59, 95% CI: 0.48, 0.71; pooled HR of mortality: 0.58, 95% CI: 0.55, 0.62) exhibited decreased risks of both CVD and mortality. When defining accelerated aging by KDM age, the results remained consistent with those of PhenoAge. Conclusions Accelerated aging is a significant risk factor for CVD and mortality. Recovering from or delaying accelerated aging, or maintaining non-accelerated aging, was associated with reduced risks of CVD and mortality. Graphical Abstract

Organelles spit out DNA contaminated with damaging components, leading to the activation of inflammatory enzymes, mouse experiments show.

The testis, with the highest number of transcriptionally active genes among human tissues, offers a unique window into how aging affects complex gene regulation. Recent advancements in single-cell RNA sequencing have enabled multi-species studies of aging-related transcriptome changes in testes. However, a comprehensive aging-related cross-species platform for analyzing testicular single-cell transcriptomes remains absent. To address this gap, we developed Aging-TCA (Aging-related Testicular Cell Atlas, available at http://tca.xielab.tech/)— a comprehensive online platform containing aging-related testicular single cell and spatial transcriptome profiles from human, cynomolgus monkey, mouse, and zebrafish across 89 samples and over 460, 000 testicular cells, nuclei or spots. Aging-TCA provides versatile tools for temporal and spatial analyzing testicular aging, including aging-related testicular gene expression visualization, cell-cell communication comparisons, cell-trajectory analysis, gene regulatory network analysis, testicular cell type auto-identification, time-series analysis, and spatial transcriptome comparisons. In summary, we provide a novel platform Aging-TCA for advancing cross-species research into testicular aging, facilitating future investigations in this field.

AbstractBackground. To estimate biological age, we developed a proteomic aging clock in cancer-free participants (CaPAC) and examined its association with

Aging | doi:10.18632/aging.206299. Francesco Neri, Shuyuan Zheng, Mark A. Watson, Pierre-Yves Desprez, Akos A. Gerencser, Judith Campisi, Denis Wirtz, Pei-Hsun Wu, Birgit Schilling

Cellular senescence has gradually been recognized as a key process, which not only inhibits the occurrence of early tumors but also promotes advanced malignant progression through secretory and immunomodulatory functions. Initially, cellular senescence manifested as irreversible cell cycle arrest, but now it encompasses a broader phenotype regulated by the p53-p21CIP1 and p16INK4A-Rb pathways. Although secretory phenotypes related to aging can recruit immune effectors to clear new tumor cells, persistent senescent cell populations often trigger chronic inflammation, promoting immune escape and fibrosis. In this review, we first discuss the molecular underpinnings of cellular senescence, highlighting its induction pathways and diverse physiological or pathological roles. We then examine the composition of the tumor microenvironment, where senescent cells accumulate and secrete pro-inflammatory cytokines, reshaping immune surveillance and extracellular matrix architecture. Against this backdrop, we explore how aging clocks refine our understanding of individual susceptibility to malignancy by distinguishing biological from chronological aging. We also present current therapeutic prospects, including senolytic agents targeting senescent stromal cells that promote tumor growth, and the utilization of aging clock metrics to tailor immunotherapies more effectively for older patients. Finally, we consider the major challenges facing clinical translation, from standardizing multi-omics data pipelines to clarifying the ethical implications of measuring biological age. By bridging senescence biology with geroscience and cutting-edge oncology, we posit that aging clocks may catalyze a transformation in cancer care, enabling more personalized, effective, and age-conscious treatment strategies.

Aging | doi:10.18632/aging.206318. Takashi Ohira, Naoyuki Kawao, Yuya Mizukami, Kiyotaka Okada, Akihito Nishikawa, Hisatoshi Yamao, Ayaka Yamada, Hiroshi Kaji

Aging is a complex process resulting in a decline in organ function. Here the authors proposes that chronic activation of tissue damage response mechanisms drives aging, with aged organs displaying features similar to those seen after acute injury. This provides a unifying framework for understanding the aging process and suggests new directions for treating age-related diseases.

The pace of organ ageing varies substantially between individuals, yet drivers of variability remain poorly understood. This gap is critical, given only 20-30% of longevity is genetically inherited[1]...

Hydrogen sulfide (H2S) plays a crucial role in various physiological processes and has been implicated in modulating aging through its impacts on oxidative stress and cellular health. This study investigates the evolutionary dynamics of the cystathionine-β-synthase (CBS), the cystathionine-ƴ-lyase (CSE), and the 3-mercaptopyruvate sulfurtransferase (3-MST) genes, involved in endogenous H2S production. We investigated CBS, CSE, and 3-MST in long-lived mammals, focusing on the naked mole-rat (Heterocephalus glaber). We hypothesized that these genes would exhibit signs of positive selection linked to extended lifespan. Codon-based evolutionary models were used to compare these genes across 114 mammalian species. Our results revealed a relaxation of purifying selection instead of positive selection in CSE, but not CBS and 3-MST, in long-lived mammals, suggesting an accumulation of mutations that enhance physiological functions related to longevity. In the naked mole-rat, CSE exhibited clear signs of positive selection, particularly in residues G116A and T118V, associated with increased protein stability and enhanced binding affinity to the cofactor pyridoxal-5′-phosphate (PLP). These mutations possibly improve CSE catalytic efficiency and potentially H2S production, supporting the naked mole-rat’s unique adaptations to its subterranean habitat and contributing to its remarkable lifespan. Our findings indicate a potential correlation between longevity and selection on the CSE gene, but not the CBS and 3-MST genes, highlighting the complex role of H2S in aging and cellular health. The study provides new insights into the molecular mechanisms underlying lifespan extension in long-lived mammals and underscores the potential adaptive significance of H2S biogenesis in the naked mole-rat.

Small study suggests uniQure drug could be first successful treatment for devastating brain disorder

YouTube video by RAZOR Science Show

In multiple sclerosis, smoldering inflammation contributes to clinical progression. Using multi-omics data, here the authors link chronic inflammation to senescence-like processes and cellular network changes, suggesting a potential therapeutic target.

Aging amplifies the mutagenic potential of short, inverted repeats in mice. The increase in point mutations in the spleen and large deletions in the brain with age highlights distinct pathways across...

The evolutionary biology of aging is fundamental to understanding the mechanisms of aging and how to develop anti-aging treatments. Thus far most evolutionary theory concerns the genetics of aging wit...

Senescent cells accumulate extranuclear DNA fragments that are recognized by the cyclic GMP-AMP synthase (cGAS) and its effector protein stimulator of interferon genes (STING), which promotes express....

The contribution of the extracellular matrix and its degradation to the aging process is not well understood. Here, the authors show that degraded elastin fragments, which increase in the circulation with age, promote aging, while counteracting elastin fragment signals alleviates inflammation, promotes healthy aging and extends lifespan.

Tests on Maria Branyas Morera, who was world’s oldest person before she died aged 117, gave doctors a trove of discoveries

EXCLI Journal - Experimental and Clinical Sciences, International Online Journal for Advances in Sciences

YouthBio receives positive FDA feedback on therapy designed to restore youthful gene expression patterns and address drivers of Alzheimer’s.

Background Aging is characterized by the decline in biological functions, accompanied by changes in gene-to-gene transcriptional coordination, which can be estimated by expression coordination in gene transcriptional network. Notably, gene networks and coordinated expression relationships (CERs) showed inter-individual variability, while personalized aging-related gene expression coordination dynamics in human cohorts have yet to be investigated. Methods In this study, we constructed 15,933 personalized transcriptional networks across 26 tissues from 967 donors aged 20 to 80 years old, using the sample-specific network (SSN) framework based on data from the Gene-Tissue Expression (GTEx) project. Results We identified gene–gene CERs and characterized their age-dependent dynamic trends across tissues, observing a universal trend of increased gene-to-gene coordination loss during aging across tissues. The count of lost CERs is also positively correlated with individual-level aging and senescence-related molecular phenotypes. Notably, we revealed that the lost CERs have potential as biomarkers for individual aging and health status. In addition, we identified gene coordination loss events exhibiting significant positive correlation with age, defined as aging-related lost relationships (ARLRs), which may be functionally associated with pathways related to proteolytic processes. Finally, we showed that ARLRs may contribute to deleterious effects and increased pathogenicity through gene dosage imbalances. Conclusions This study establishes, for the first time, a connection between the loss of gene-to-gene expression coordination and individual-level aging progress. It provides proof-of-principle evidence for using lost gene coordinated expression relationships as biomarkers of healthy aging and highlights the potential risks associated with coordination loss in specific biological pathways during aging.

Parental lysosomes modify epigenetic signaling to influence offspring life span